Heterocyclically substituted perhydrocarbazoles



Patented June 4, 1935 No Drawing. Applic N0. 602,400.

Ehrhart, assignors to Win New York, N. Y., a corpor HYDROCARBAZOLES V Max. Bockmiihl, Walter Krohs, and Gustav 2 Claims.

The present invention relates. to organic compounds containing radical, more particularly to com followinggeneral formula: I

carbazole or perhydroacridine compounds by exchanging their. imine-hydrogen according to general known methods for a basic group, into compounds containing several nitrogen atoms in 1 which the i r d .n t oeeaat mo atom or are bound by means of an aliphatic, cyclic-0r alicyclic. radicle to; the imino group of the perhydrogenated heterocyclic radicle, or by convertds suita ble intermediate products, derived from penhydrocarbazole or, perhydroacridin imine hydrogen, into-sue ing-according to known, metho CH: CH

a heterocyclic hydrogenated wherein 11. means 0 orl, Z,stands for substituted or unsubstitutedalkyl oryalkoxy, R stands for a five-membered heterocyclic or hydrogenated heterocyclic radical containing nitrogen, and X may stand for alkyl oralkoxy substituting one of the hydrogen atoms of the cHz-groups.

We have found that compounds of the above constitution are obtained'by convertmg perhydroseveral nitrogen atoms.

" These substances can be producedQfor instance, by causing perhydrocarbazole or perhydroacridine to react with a halogen-alkyl-amine,

e by, substitution ofthe h compounds containing ounds of the y .X I GEL.

which may be used in the form of the free base or in the form of a salt. The new compounds can also be prepared from perhydrocarbazole 1r perhydroacridinein other ways, for instance, by converting these perhydrogenated hetercyclic compounds by means of an alkylene oxide, halogen hydrin or alkylene dihalideinto the corresponding perhydrocarbazole- '5 TheN-hydroxy causing the latter "compound containi for N-hydroxyal kylor N-halogen-alkyl- (or acridine) compound and to reactwith a suitable basic ng a reactive group. As far as,

instance, N;-aminoalkylperhydrocarbazole- (or acridine) ecompoun still contain free, hydro groups, these compoun to react witha c0 group, for instance,

mpoun ds are obtained, which genfatoms in the amino ds can further be caused d containing a reactive containmghalog'en.

alkylperhydrocarbazoles, for in- Frankfort-on-the-Main,

throp Chemical Company, Inc

ation of New York ation March 31, 1932, Serial In Germany April 4, 1931 stance, produced from halogen hydrinsjcanbe caused to react in the form of the alcoholates with a like'result with compounds which contain a reactive halogen and asic character or are capable of a compound of basic character rmation, for instance, by reeither have a, b conversion into:

by chemical transfo duction.

From the foregoingjt will be understood that ting the nitrogen of the percompounds with the be of any nature. It

the memberconnec hydrogenated heterocyclic introduced nitrogen may may,.for instance,;b,e asimple aliphatic chain of carbon atoms, such as ethyl, propyl, which may be substituted, 'or a chain containing both carbon atoms and various other elements, such as oxygen, su1fur-or nitrogen, for instance, ethoxy. The connectingmember may'likewise consist of a cyclicrradicle' or it may be "a combination of uble' in water, an soluble in water.

'The following ,exa tion, the parts being by weighty- (1 l 1 -perhydrocarbazylethylimidazole PATENT OFFICE QHE'r iitccycLicALLY sunsmumnrm.

Germany, it

i CH-N l2 partsof chlorethylperhydrocarbazole and 7 parts of imidazole are heated for 2 hourson the .5

perhydrocarbazole and wholly or partly of v s are valuable therapeutic substances; they are in the form of the free bases compounds which are diflicultly'soluble or insold form hydrochlorides which are mples milstm ethe invensteam bath. After cooling, the mass is mixed with Water and caustic soda solution and the Whole is extracted with ether. The other extract is dried, the ether removed and the residue distilled under reduced pressure, The perhydrocarbazylethylimidazole distills at 198 C.-205 C. at 3 mm. "pressureand forms a 'dihydrobromi'de melting at 238 C.

(2) 1-perhydrocarbazylethyl-5-methylpyrazoline -18 parts of chlorethylperhydrocarbazole and "13 partsof 5-methylpyrazoline are heate'dfor l'hour on :the steam bath. After cooling the mass .is mixed with water and caustic sodasolution, the baseis extracted with ether -andtpurified by Histillation under reduced pressure. The .product is a yellowish-oil which boilsat173 C.-1'8'0f C. at a pressure of 4 mm. It formsta monohydrobro- -midebeing a colorless substance which melts at T 30 parts of N hydroxyethylperhydrocarbazole, 5 parts of sodami'de and "150 parts of toluene-are heated to boiling for 2 "hours, while stirring, 23 parts -of chlorocafieine are, added in ffour or vfive portions, and "the whole "is 'heated"to "boiling for 'a' furth'er "8 hours. After 'co'olingfi'the mass is mixed with water and the "toluene solution is shaken with hydrochloric :acid. "I'he "product is precipitated "from the hydrochloric "acid solution by means ofsodium carbonate, and'extracted 'withether. "The ethereal "extract is dried by means of T potassium carbonate, the ether is distilled and the residue is dissolved in acetone. O'n' neutralizing the 'a'cetone' solution with alcoholic hydrochloric acid a hydrochloride "isob- 'tained "which, when recrystallized from "water, melts at 221C.

('4) ibipe'rlty'drocaflni213)lethlme CH: CH1 e. H CH, H: :11 {on JHI CH1 CH1 v :;6-,parts-ofethylenebromide -M. parts of; perhydrocarbazole and 25 parts of benzene are heated for 2 hours on the steam bath. The mass is then mixed with 100 parts of benzene, the separated perhydrocarbazole hydrobromide is filtered by suction and the benzene is removed from the filtrate 'by distillation. The residue is recrystallized from alcohol and constitutes the new base of melting point 111 C.

2-imino-3-perhydrocarbazyl-ethyl-4- imethybthiazole-dihydride (4:5)

CH-S

of the dihydrochloride which, recrystallized from alcohol, melts at 224 C.

(6) 1-perhydrocarbazylethyl-2-methylimidazoledihydride-(4:5) ea- N it'tm .lt-om "ICE: 7 J+HI $59 K {0H, in cn,

;o 1 c 1 '14 "partsof 2 methylilriitlaizline and 18 i 0! N-'chlorethylperhydrocarbazole -are '-heat'ed {Ior "2"hours on thesteambath. 'The reaction product is fniixed with caustic soda solution -"and th'e ne'w "base is extractedwith ether'and purifie'd byadistillation *unilerweduced pressure. It boils at j'220-'C. at 3 mm. pressure and forms a dihydrobromide melting '-a;t '-211 "C.

"Haj H 'HKH1 dfiz Cl C: parts :or "2-methylpyrazoline iand 116 Traits of ,hlorethylperhydroacridine are heated I01 jone Ihouron the steamlbath. "Thetmassiisithenmixed with 100 .parts of'a'cetoneandtreated with alcof holic hydrochloricaci'd until thereaction" to.Con- .go paper is strongly acid. 'iflfhe dihydrochloride of "the .condensation vproduct separates. '.'Since it has ayry:strongtacid reaction, thelbas'e'is sep- -aratedifrom its aqueous-solution; it is extracted perhydroacridylethyl-5-mthylpyrazoline with ether, the ether residue is dissolved in acetic ester and mixed with such a quantity of alcoholic hydrochloric acid that the reaction to litmus paper is just alkaline. The monohydrochloride is precipitated which, after recrystallization from acetone and acetic ester, melts at 191 C.

We claim:

1. The 1-perhydrocarbazylethyl-5-methylpyrazoline of the following formula:

being a yellowish oil boiling at 173 C. to 180 C.

at a pressure of 4 mm., forming a monohydrobromide, a colorless substance melting at 187 C., said product being a useful therapeutic.

2. The compounds of the following formula:

/Cg2 /CEI $111 CH-?H (3H1 on, as CH CH: C: 1? OH:

| H: Ni wherein N1 is part of a five-membered heterocy- 15 clic unsaturated or saturated radical, said compounds being difilcultly soluble or insoluble in water, forming hydrohalides soluble in water and being useful as therapeutics.

MAX BOCKMUI-IL. 20

WALTER KROHS. GUSTAV EHRHART. 

